Pluripotent stem cell morphogenesis in engineered hydrogels as a model of early human development

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Abstract/Contents

Abstract
Human embryogenesis involves a series of complex morphogenetic events, wherein human pluripotent stem cells (hPSCs) give rise to all the tissues in the human body. Mechanisms of embryogenesis cannot be studied directly in human embryos due to ethical concerns and technological limitations. Yet, these mechanisms hold the key for taking stem-cell-based therapies to the clinic. To tackle this, there has been a tremendous effort recently toward developing hPSC-based models of the embryo, but current studies lack mechanistic insights as well as reproducibility, due to use of extracellular matrices such as Matrigel which are poorly defined and heterogeneous with limited tunability of matrix properties. In this dissertation, I will first demonstrate the use of engineered alginate hydrogels for studying the impact of hydrogel mechanical properties on hPSC behavior, with hPSCs forming human epiblast-like structures in specific hydrogels. The human epiblast forms a central fluid-filled lumen during embryogenesis which is crucial for proper establishment of the body axes. Using the hPSC-based model of human epiblast, I next unearth the mechanism of epiblast lumen formation. Overall, this body of work demonstrates the power of embryo models and engineered hydrogels, and greatly advances our understanding of the self-organization mechanisms that drive human embryo development.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2023; ©2023
Publication date 2023; 2023
Issuance monographic
Language English

Creators/Contributors

Author Indana, Dhiraj
Degree supervisor Chaudhuri, Ovijit
Thesis advisor Chaudhuri, Ovijit
Thesis advisor Bhutani, Nidhi
Thesis advisor Levenston, Marc Elliot
Degree committee member Bhutani, Nidhi
Degree committee member Levenston, Marc Elliot
Associated with Stanford University, School of Engineering
Associated with Stanford University, Department of Mechanical Engineering

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Dhiraj Indana.
Note Submitted to the Department of Mechanical Engineering.
Thesis Thesis Ph.D. Stanford University 2023.
Location https://purl.stanford.edu/pf792dk2298

Access conditions

Copyright
© 2023 by Dhiraj Indana
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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